Transcription Regulation and Biological Function of NAG1

NAG1的转录调控及生物学功能

• 批准号: 6799937
• 负责人: SEUNG Joon BAEK
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-08 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6799937
• 关键词: antiinflammatory agents; apoptosis; carcinogenesis inhibitor; chemoprevention; gene expression; genetic promoter element; genetic transcription; genetically modified animals; laboratory mouse; nonsteroidal antiinflammatory agent; recombinant proteins

DESCRIPTION (provided by applicant) Nonsteroidal antiinflammatory drugs (NSAlDs) have been used for the treatment of inflammatory disease. NSAlDs also have anti-tumorigenic activity. An anti-tumorigenic protein, called NSAID activated gene-1 (NAG-1), mediates one molecular mechanism for NSAID-induced anti-tumorigenic activity. It is possible that NAG-1 may contribute to anti-tumorigenic and anti-inflammatory activity produced by NSAlDs. Therefore, the elucidation of transcriptional regulation and the biological functions provides a novel mechanism to better understand cancer and inflammation. The research objectives are to study how NSAlDs regulate NAG-1 gene expression, and also how environmental factors may affect-NAG-1 gene regulation to prevent cancer and inflammation. Two specific aims are involved in this research. First, the promoter of NAG-1 gene will be used to elucidate its NSAID responsiveness and then cloning the NSAID responsive binding protein. Secondly, the biological function of NAG-1 will be assessed using purified recombinant NAG-1 protein and NAG-1 overexpressing transgenic mice, to elucidate its anti-tumorigenic and anti-inflammatory activities. This proposal also seeks to address how NSAlDs regulate anti-tumorigenesis, and whether other factors, believed to modulate tumor development, could do so by altering gene regulation. This study may also provide new insights into how chemical and environmental factors influence cancer development and lead to the development of novel family anti-tumorigenic compounds, which are not cyclooxygenase (COX) inhibitors. Cancer and inflammation are certainly environmentally relevant problems and thus this project will provide new clues to aid in the understanding of how these drugs alter tumor development.

描述（由申请人提供） 非甾体类抗炎药（NSAlD）已用于治疗炎症性疾病。 NSAID 还具有抗肿瘤发生活性。 一种抗肿瘤发生蛋白，称为 NSAID 激活基因 1 (NAG-1)，介导 NSAID 诱导的抗肿瘤发生活性的一种分子机制。 NAG-1可能有助于NSAID产生的抗肿瘤发生和抗炎活性。 因此，转录调控和生物学功能的阐明为更好地理解癌症和炎症提供了新的机制。 研究目标是研究NSAID如何调节NAG-1基因表达，以及环境因素如何影响NAG-1基因调节以预防癌症和炎症。 这项研究涉及两个具体目标。 首先，NAG-1基因的启动子将用于阐明其NSAID反应性，然后克隆NSAID反应性结合蛋白。 其次，将使用纯化的重组NAG-1蛋白和NAG-1过表达转基因小鼠评估NAG-1的生物学功能，以阐明其抗肿瘤和抗炎活性。 该提案还试图解决 NSAID 如何调节抗肿瘤发生，以及其他被认为调节肿瘤发展的因素是否可以通过改变基因调节来实现这一点。 这项研究还可能为化学和环境因素如何影响癌症发展提供新的见解，并导致新型家族抗肿瘤化合物（非环氧合酶（COX）抑制剂）的开发。 癌症和炎症当然是与环境相关的问题，因此该项目将提供新的线索，帮助了解这些药物如何改变肿瘤的发展。